The objective of this research is to develop methods for turning the brain synaptic membrane inside-out. Two general methods will be tested. Synaptic plasma membranes will be isolated and incubated in solutions which should cause the membranes to turn inside-out as has been shown for red blood cell membranes. Also, synaptosomes will be attached to beads and lysed. The resulting bead-bound membranes will be purified and their purity, orientation, intactness, and the extent of membrane rearrangements will be determined. An inside-out brain synaptic plasma membrane preparation will enable investigators to study the mechanism and regulation of neurotransmitter release and other synpatic functions from the perspective of the normally inaccessible interior of the synapse.